HALO Trial: Haloperidol vs Olanzapine in Hyperactive Delirium in Palliative Care Patients; A Multi-Centre, Randomised-Controlled Trial

NCT04833023 | Recruiting Phase 3 DMC

• 1 other identifier: PalC-RG-20/P001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 3

Brief Summary

1. 1.Background and Clinical Need:
2. 2.Aims/Hypotheses:
3. 3.Methods:
4. 4.Significance to palliative care The results of this study will advance the knowledge of delirium management worldwide with regards to the efficacy of Haloperidol and Olanzapine in managing hyperactive delirium in patients with advanced cancer or end-stage organ disease.

Conditions

Haloperidol; Advanced Cancer; Hyperactive Delirium; Olanzapine; End-stage Organ Disease

Outcome Measures

Primary Outcomes (1)

• Change in Richmond Agitation and Sedation Scale (RASS) score

  The change in Richmond Agitation and Sedation Scale (RASS) score 8 hours after administration of either Haloperidol and Olanzapine. Minimum value is -5 which represents that the patient is in hypoactive delirium and is unarousable and maximum value is +4 with the higher score representing that the patient is in hyperactive delirium and is combative. The aim of the study is to reduce the hyperactive delirium to a score of 0 which represents patient is alert and calm.

  8 hours

Secondary Outcomes (10)

• Comparing Patient and Family's concurrence on state of delirium with of the Diagnosis of Delirium from Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for delirium.

  72 hours

• Mean dose used of Haloperidol and Olanzapine

  72 hours

• Mean Time to control of Hyperactive Delirium

  72 hours

• Rescue Psychotropic (Mean Doses): Midazolam

  72 hours

• Side-effects of Study Medications

  72 hours

Study Arms (2)

Haloperidol Arm

ACTIVE COMPARATOR

Haldol 2mg/ml oral solution

Drug: Haldol 2mg/ml oral solution

Olanzapine Arm

ACTIVE COMPARATOR

Olanzapine Actavis 5mg orodispersible tablet

Drug: Olanzapine Actavis 5mg orodispersible tablet

Interventions

Haldol 2mg/ml oral solution DRUG

Starting dose: 1mg Maximum Dose within 24 hours: 6mg Doses can be escalated every 2 hourly to the maximum doses allowed within 24 hours. If maximum dose of Haloperidol has been reached for the day (within 24 hours), rescue dose of Midazolam 2mg can be used (2mg Q2H PRN).

Haloperidol Arm

Olanzapine Actavis 5mg orodispersible tablet DRUG

Starting dose: 2.5mg Maximum Dose within 24 hours: 15mg Doses can be escalated every 2 hourly to the maximum doses allowed within 24 hours. If maximum dose of Olanzapine has been reached for the day (within 24 hours), rescue dose of Midazolam 2mg can be used (2mg Q2H PRN).

Olanzapine Arm

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced cancer or end-stage organ disease
• Age ≥ 21 years old
• Fulfil All Three Diagnosis of Delirium:
• Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for delirium
• Memorial Delirium Assessment Scale (MDAS)©1996 \>/= 13
• Richmond Agitation-Sedation Scale (RASS) Score +1 to +3
• Able to consume medications orally
• Prognosis \> 48 hrs (Clinician Estimate)

You may not qualify if:

• Parkinson's Disease or Vascular Parkinsonism
• Patient with dementia
• Chronic Schizophrenia on regular Anti-psychotic medications
• Taking any regular Benzodiazepines\* or any Anti-psychotic\*\* medications
• Known allergy to Haloperidol or Olanzapine
• History of Substance Abuse
• Known Prolonged corrected QT interval (QTc) Syndrome (In Patient's Medical History)
• Prognosis \< 48 hours (Clinician's Estimate)
• Unable to consume oral medications
• Richmond Agitation and Sedation Scale (RASS) Score +4 (Too agitated and will require Parenteral Anti-psychotics and/or Benzodiazepines)
• Pregnancy \* e.g. Lorazepam, Alprazolam, Clonazepam, Midazolam \*\*e.g. Haloperidol, Risperidone, Quetiapine, Olanzapine

Sponsors & Collaborators

• Tan Tock Seng Hospital: lead

Study Sites (3)

Tan Tock Seng Hospital

Singapore, 308433, Singapore

RECRUITING

Dover Park Hospice

Singapore, 308436, Singapore

RECRUITING

St. Andrew's Community Hospital

Singapore, 529895, Singapore

RECRUITING

Related Publications (12)

• Hosie A, Davidson PM, Agar M, Sanderson CR, Phillips J. Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: a systematic review. Palliat Med. 2013 Jun;27(6):486-98. doi: 10.1177/0269216312457214. Epub 2012 Sep 17.

  PMID: 22988044 BACKGROUND

• Watt CL, Momoli F, Ansari MT, Sikora L, Bush SH, Hosie A, Kabir M, Rosenberg E, Kanji S, Lawlor PG. The incidence and prevalence of delirium across palliative care settings: A systematic review. Palliat Med. 2019 Sep;33(8):865-877. doi: 10.1177/0269216319854944. Epub 2019 Jun 11.

  PMID: 31184538 BACKGROUND

• Hui D. Delirium in the palliative care setting: "Sorting" out the confusion. Palliat Med. 2019 Sep;33(8):863-864. doi: 10.1177/0269216319861896. No abstract available.

  PMID: 31395002 BACKGROUND

• Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available.

  PMID: 16540616 BACKGROUND

• Skelton L, Guo P. Evaluating the effects of the pharmacological and nonpharmacological interventions to manage delirium symptoms in palliative care patients: systematic review. Curr Opin Support Palliat Care. 2019 Dec;13(4):384-391. doi: 10.1097/SPC.0000000000000458.

  PMID: 31490322 BACKGROUND

• Zipser CM, Knoepfel S, Hayoz P, Schubert M, Ernst J, von Kanel R, Boettger S. Clinical management of delirium: The response depends on the subtypes. An observational cohort study in 602 patients. Palliat Support Care. 2020 Feb;18(1):4-11. doi: 10.1017/S1478951519000609.

  PMID: 31506133 BACKGROUND

• Hui D, Frisbee-Hume S, Wilson A, Dibaj SS, Nguyen T, De La Cruz M, Walker P, Zhukovsky DS, Delgado-Guay M, Vidal M, Epner D, Reddy A, Tanco K, Williams J, Hall S, Liu D, Hess K, Amin S, Breitbart W, Bruera E. Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial. JAMA. 2017 Sep 19;318(11):1047-1056. doi: 10.1001/jama.2017.11468.

  PMID: 28975307 BACKGROUND

• Breitbart W, Alici Y. Agitation and delirium at the end of life: "We couldn't manage him". JAMA. 2008 Dec 24;300(24):2898-910, E1. doi: 10.1001/jama.2008.885.

  PMID: 19109118 BACKGROUND

• Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, Sanderson C, Hardy J, Le B, Eckermann S, McCaffrey N, Devilee L, Fazekas B, Hill M, Currow DC. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jan 1;177(1):34-42. doi: 10.1001/jamainternmed.2016.7491.

  PMID: 27918778 BACKGROUND

• Boettger S, Friedlander M, Breitbart W, Passik S. Aripiprazole and haloperidol in the treatment of delirium. Aust N Z J Psychiatry. 2011 Jun;45(6):477-82. doi: 10.3109/00048674.2011.543411.

  PMID: 21563866 BACKGROUND

• Lin CJ, Sun FJ, Fang CK. An open trial comparing haloperidol with olanzapine for the treatment of delirium in palliative and hospice center cancer patients. J Internal Med Taiwan 2008; 19:346-354.

  BACKGROUND

• Bush SH, Grassau PA, Yarmo MN, Zhang T, Zinkie SJ, Pereira JL. The Richmond Agitation-Sedation Scale modified for palliative care inpatients (RASS-PAL): a pilot study exploring validity and feasibility in clinical practice. BMC Palliat Care. 2014 Mar 31;13(1):17. doi: 10.1186/1472-684X-13-17.

  PMID: 24684942 BACKGROUND

MeSH Terms

Interventions

Haloperidol; Solutions

Intervention Hierarchy (Ancestors)

Butyrophenones; Ketones; Organic Chemicals; Pharmaceutical Preparations

Study Officials

• Mervyn Koh

  Tan Tock Seng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mervyn Koh

CONTACT

+6597678996; mervyn_koh@ttsh.com.sg

Allyn Hum

CONTACT

+6581263205; allyn_hum@ttsh.com.sg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study statistician will be blinded to the treatment allocation and outcome assessments (for example, Richmond Agitation and Sedation Scale).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 6, 2021
• Study Start: May 18, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (3)